Role of Nitric Oxide in the Colon of Patients With Slow-Transit Constipation

PURPOSE: The cause of dysmotility in patients with slow-transit constipation is unknown. Nitric oxide has recently been shown to be a neurotransmitter in the nonadrenergic, noncholinergic inhibitory nerves of the human gut. To clarify the physiologic significance of nitric oxide in the colon of patients with slow-transit constipation, we investigated the enteric nerve responses in lesional and normal bowel segments derived from patients with slow-transit constipation and patients who underwent colon resection for colonic cancers. METHODS: Twenty-six preparations were taken from colonic lesions in eight patients with slow-transit constipation (2 men; age, 23 to 69 (mean, 44.8) years). Forty-two preparations were taken from the normal colons of 14 patients with colonic cancer (8 men; age, 40 to 66 (mean, 52.4) years). A mechanographic technique was used to evaluate in vitro muscle responses to electric field stimulation before and after treatment with various autonomic nerve blockers, NG-nitro-L-arginine, and L-arginine. RESULTS: The colons of patients with slow-transit constipation were more strongly innervated by nonadrenergic, noncholinergic inhibitory nerves than were normal colons (P <0.05). Nitric oxide was found to act on both normal and slow-transit constipation colons. The colons of patients with slow-transit constipation were more strongly innervated by nitric oxide nerves than were normal colons (P < 0.01). Responses to electric field stimulation were the same in each case among the normal colons and were also the same in each case among the slow-transit constipation colons. CONCLUSION: These findings suggest that an increase of nitric oxide mediates nonadrenergic, noncholinergic inhibitory nerves and plays an important role in the dysmotility observed in the colons of patients with slow-transit constipation.